Opposite Interplay Between the Canonical WNT/β-Catenin Pathway and PPAR Gamma: A Potential Therapeutic Target in Gliomas

• 来源期刊: 神经科学通报（英文版）
• 年，卷（期）: 2018,（3）
• 页码范围: 573-588
• 页数: 16页
• 语种: 英文

摘要

In gliomas,the canonical Wingless/Int (WNT)/β-catenin pathway is increased while peroxisome proliferator-activated receptor gamma (PPAR-γ) is downregulated.The two systems act in an opposite manner.This review focuses on the interplay between WNT/β-catenin signaling and PPAR-γ and their metabolic implications as potential therapeutic target in gliomas.Activation of the WNT/β-catenin pathway stimulates the transcrpfion of genes involved in proliferation,invasion,nucleotide synthesis,tumor growth,and angiogenesis.Activation of PPAR-γ agonists inhibits various signaling pathways such as the JAK/STAT,WNT/β-catenin,and PI3K/Akt pathways,which reduces tumor growth,cell proliferation,cell invasiveness,and angiogenesis.Nonsteroidal anti-inflammatory drugs,curcumin,antipsychotic drugs,adiponectin,and sulforaphane downregulate the WNT/β-catenin pathway through the upregulation of PPAR-γ and thus appear to provide an interesting therapeutic approach for gliomas.Temozolomide (TMZ) is an antiangiogenic agent.The downstream action of this opposite interplay may explain the TMZ-resistance often reported in gliomas.